Introduction Endometrial cancer (EC) is the most commonly diagnosed gynaecological malignancy in developed countries. EC comprises type I endometrioid EC and type II non-endometrioid EC, the most aggressive and with poor prognosis. Treatment options, hysterectomy, chemotherapy and combinations with radiation, have limited efficacy, and only limited options remain if the tumors relapse or metastasize. Transient Receptor Potential Vanilloid 2 (TRPV2) is often dysregulated in tumors and has been associated with altered cell proliferation, invasiveness and aggressiveness in different cancer cell lines and animal models. In this work we analysed TRPV2 expression in human type II EC biopsies and type I and II EC cell lines, and the TRPV2-dependent effects on cell migration and chemo-sensitivity in vitro. Material and Methods TRPV2 expression was evaluated in EC cell lines by RT-PCR and western blot and in EC biopsies by immunohistochemistry. TRPV2 correlation with Overall Survival (OS) and Progression-Free Survival (PFS) was evaluated by Kaplan–Meier analysis. TRPV2 transfection and activation was used to evaluate the modulation of migratory capacity, Akt expression and chemosensitivity, by wound healing, western blot and MTT assay. Results and Discussions Results show that EC malignancy correlates with high levels of TRPV2, that is associated with shorter PFS. In cells expressing low levels of TRPV2, TRPV2 transfection increased migration and Akt expression, confirming that TRPV2 increases aggressiveness. Chemosensitivity was increased in overexpressing TRPV2 cells and with a TRPV2 activator, mainly in TRPV2 transfected cells, probably because drug permeates directly through TRPV2 pore channel, like seen in another study with glioblastoma cells. Conclusion Data support the hypothesis that TRPV2 expression increases EC aggressiveness, therefore can be used as a marker for diagnosis and to optimize the therapy, with a TRPV2 agonist might being a strategy as adjuvant therapy.
TRPV2 correlates with endometrial cancer aggressiveness and its activation improves chemosensitivity
C. Aguzzi
Primo
;L. Zeppa;O. Marinelli;M. B. Morelli;C. Amantini;F. Maggi;G. Santoni;M. Nabissi
2022-01-01
Abstract
Introduction Endometrial cancer (EC) is the most commonly diagnosed gynaecological malignancy in developed countries. EC comprises type I endometrioid EC and type II non-endometrioid EC, the most aggressive and with poor prognosis. Treatment options, hysterectomy, chemotherapy and combinations with radiation, have limited efficacy, and only limited options remain if the tumors relapse or metastasize. Transient Receptor Potential Vanilloid 2 (TRPV2) is often dysregulated in tumors and has been associated with altered cell proliferation, invasiveness and aggressiveness in different cancer cell lines and animal models. In this work we analysed TRPV2 expression in human type II EC biopsies and type I and II EC cell lines, and the TRPV2-dependent effects on cell migration and chemo-sensitivity in vitro. Material and Methods TRPV2 expression was evaluated in EC cell lines by RT-PCR and western blot and in EC biopsies by immunohistochemistry. TRPV2 correlation with Overall Survival (OS) and Progression-Free Survival (PFS) was evaluated by Kaplan–Meier analysis. TRPV2 transfection and activation was used to evaluate the modulation of migratory capacity, Akt expression and chemosensitivity, by wound healing, western blot and MTT assay. Results and Discussions Results show that EC malignancy correlates with high levels of TRPV2, that is associated with shorter PFS. In cells expressing low levels of TRPV2, TRPV2 transfection increased migration and Akt expression, confirming that TRPV2 increases aggressiveness. Chemosensitivity was increased in overexpressing TRPV2 cells and with a TRPV2 activator, mainly in TRPV2 transfected cells, probably because drug permeates directly through TRPV2 pore channel, like seen in another study with glioblastoma cells. Conclusion Data support the hypothesis that TRPV2 expression increases EC aggressiveness, therefore can be used as a marker for diagnosis and to optimize the therapy, with a TRPV2 agonist might being a strategy as adjuvant therapy.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
